1. Field of the Invention
The present invention relates generally to a pharmaceutical composition comprising aqueous extracts of Anemarrhena Rhizoma, a member of the family Liliaceae, and Phellodendron Bark, a member of the family Lilium for analgesic and anti-inflammation, and its preparing method. More particularly, it relates to a pharmaceutical composition comprising mixed aqueous extracts of Anemarrhena Rhizoma and Phellodendron Bark for analgesic and anti-inflammation against chronic gastritis, arthralgia, benign prostate hyperplasia, chronic and recurrent cystitis, cervical disc, degenerative joint arthritis, rheumatoid arthritis, tennis elbow, osteoportotic pain, migraine, diabetic neuropathy pain, Rt. flank pain, etc.
2. Description of the Related Art
There are two types of pain, one of which is fast pain sensed immediately in response to stimulants and the other is slow pain sensed gradually. The slow pain results from injuries to both the skin and the internal tissue and lasts long, while the fast pain results from injuries to the skin rather than to the internal tissue. The pain is sensed through receptors distributed over the skin and tissue, especially, those for mechanical, thermal and chemical stimulants. Upon receipt of stimulation, the receptors transmit sensation to the central nerve system. Examples of the chemicals exciting the chemical type of pain receptors include bradykinin, potassium ions, acids, proteolytic enzymes, etc. Compared to the other types of sensation, the lasting pain becomes more sensitive to stimulants and develops intolerance even to a weak stimulant.
In the body system, neurons of the brain and the vertebral column secrete those substances such as morphine that elicit an analgesic effect, and regulate the pain. Examples of the analgesic substances include endorphin, enkephalin and dynorphin secreted from the brain, and serotonin and enkephalin from the vertebral column.
The existing analgesics may be classified into two categories: (a) narcotic analgesics, e.g., codeine and dihydrocodeine and (b) non-steroidal anti-inflammatory drugs (NSAIDSs), e.g., aspirin, ibuprofen and indomethacin.
The narcotic analgesics excite receptors of the central nerve system to alleviate both light and severe pains. The narcotic analgesics are used in an increased dose depending on the degree of a pain and very effective in pain relief. However, the effect of the narcotic analgesics is practically dose-dependent and results in resistance to analgesics. In the worst cases, the narcotic analgesics adversely produce a side effect of depressing the respiratory and circulatory organs.
The NSAIDS inhibits the production of prostaglandin from arachidonic acid. Thus NSAIDS not only acts to alleviate pain and platelet agglutination attendant upon particular degenerative diseases but also reduces inflammation. The NSAIDS is to some extent effective as an analgesic and anti-inflammatory agent but often leads to side effects, i.e., stomach ulcer and bleeding of digestive organs.
Recently, there is an attempt to implement a therapeutic method that involves administration of a combination of narcotic analgesics and NSAIDs in order to maximize the beneficial effects of the above-mentioned single components while avoiding the side effects thereof.
Meanwhile, inflammation refers to a response to an tissue injury caused by pathogenic microorganisms, trauma, chemicals and heat in view of restoring the injured tissue, that is, the whole local tissue response to an injury involving secretion of several mediators from the injured tissue, induction of immunocytes and recovery of the injured tissue. This process can be summarized as follows. With tissue cells damaged or destroyed, acids and chemical mediators are released. The mediators cause the dilation of blood capillaries and increase their permeability. Histamine secreted from mast cells or basophiles initiates the response of blood vessels, and serum kinin produced from alpha-2-globulin of blood serum mediates the long-acting response of blood vessels through the blood coagulation mechanism. The blood capillary dilation increases the blood flow, and causes heat and redness. The increased permeability of the blood capillaries cause blood cells, proteins and fluids to exude into surrounding tissues, leading to swelling. Such exudation can accelerate further destruction of cells, and the increased blood pressure stimulates peripheral nerves to cause pain. The pain increases due to secretion of kinin and acids. Other mediators secreted from the tissue include serotonin, prostaglandin, reactants of the complement system, and lymphokine secreted from T-cells.
As fluid exudes from the capillaries, leukocytes (i.e., neutrophils and monocytes) migrate to the damaged region and digest or dissolve inflammation-causing substances to recover the damaged area. Another important cells in the inflammatory reaction are monocyte-originated macrophages that also participate in phagocytosis and rapidly proliferate when the tissue is damaged. Fusion of the macrophages or amitotic division of large fragments produces giant cells.
The inflammatory reaction occurs locally or entirely in the body system. In some cases, pyrogens secreted from bacteria stimulate the thermoregulatory center in the brain and produce a fever which, in turn, raises metabolic rate, decreases appetite and results to depletion of somatic tissue with muscle and body fat. Fluid losses may result in dehydration. Lymph fluid absorbs fluid and the protein exuded from the blood capillaries, and transports them to the lymphnode, which causes lymphadenitis characterized by lymphnode enlargement and pain.
As described, inflammation is a primary mechanism of the body system to repair tissue damage or protect against latent infection. However, an untimely or chronic inflammation reaction can result in pain or diability.
There can be used two types of antiinflammatory medications, the one of which involves inhibiting production and exudation of inflammatory cells and the other involves reducing secretion of inflammation mediators. The currently used medical agents may be divided into NSAIDs, capable of producing both analgesic and inflammatory effects as described above, and steroidal anti-inflammatory drugs. The NSAIDs are widely spread as analgesic and inflammatory agents and have a mechanism of inhibiting production of prostaglandin from arachidonic acid. Corticosteroids used against inflammation not only inhibit generation of prostaglandin but also act on beta-adrenergic receptors of leukocytes to inhibit secretion of inter-leukins (ILs) and reduce permeability of the blood vessels, which in turn inhibits exudation of blood and inflammatory cells. Despite the therapeutic effects, corticosteroids have been reported to produce a number of side effects, such as increasing the size of erythrocytes, weight gain, accelerating progression of osteoporosis and weakening blood capillary, raising blood pressure and stomach ulcer. Cromolyn sodium is also used as an inflammatory agent involving stabilization of the cytoplasmic membrane of mast cells and inhibiting activation of macrophages, but produce a number of side effects.
The following description deals with two cases of benign prostate hyperplasia and chronic cystitis in detail.
Benign prostate hyperplasia(BPH) is one of the prevailing diseases among at least 50% of aged males over fifty and estimated as a degenerative disease involving the enlargement of prostate gland due to intact androgen supply as the man gets old. In the early stage of forties, nodules can generate in the transition(grandula) and periurethral zones (stromal). The nodules formed in the transition zone continuously grow into the major part of the main mass of the BPH, in which case the central and peripheral zones are compressed and fibromuscular tissue develops between the BPH tissue. This progresses over several years and symptoms appear as the enlarged prostate obstructs the urinary track.
The symptoms of benign prostate hyperplasia can be divided into "obstructive" symptoms caused by obstruction of the urethra with BPH, and "irritative" symptoms caused by inflammation or infection of the urinary track. The obstructive symptoms include weak stream, straining, prolonged micturition, postmicturitional dribbling, urinary retention and paradox incontinence. The irritative symptoms include urgency, frequency, nocturia, urge incontinence and suprapubic pain. The irritative symptoms are usually accompanied with infection and the patient suffering from these irritative symptoms is hard to be satisfied even after a prostatectomy.
The recent therapies of benign prostate hyperplasia such as prostatectomy or removal of the dilative prostate using a laser beam are a temporary treatment that cannot inhibit lasting dilation of the prostate. Therapeutic drugs used against benign prostate hyperplasia are alpha-adrenergic antagonists inhibiting tone of the prostate or reducing androgen hormones production to prevent prostate dilation, but cannot be used in a continuous manner due to side effects.
On the other hand, chronic cystitis is a quite common disease to menopausal and post-menopausal women, and primarily caused by viruses and stress. This disease has limitations on the treatment because it is easy to become chronic and recur. Chronic cystitis is accompanied with symptoms similar to those of benign prostate hyperplasia, i.e., frequency, nocturia, urge incontinence, and so forth. In most cases, trimethoprime-sulfaethoxazol (4 single-strength tablets) and fluoroquinoline (norflxacin, ciprofloxacin, ofloxacin) are used for treatment of acute cystitis free from a complication, caused by infection of E. coli. Chronic or recurrent cystitis or urinary track infection with complications (including cystitis) usually result from infection through E. coli, Klebsiella, Proteus, Pseudomonas, etc. Because most these infective viruses are antibiotic-resistant strains, a long-term treatment is required using antibiotics or antibacterial agents such as imipenem, cephalosporine, aminoglycoside or ceftraxone. The related diseases are ready to recur after a long-term treatment, and hence not curable completely. The diseases also produce a number of side effects.
Trimethoprime-sulfaethoxazol is a widely used antibacterial agent with side effects involving skin rash, central nerve disorder, and an increased toxicity to blood picture, gastrointestinal system, liver and kidney. Fluoroquinoline is a quinoline-based fluoride and causes adverse side effects such as nausea, abdominal sickness, headache and vertigo and, for the worse, skin rash and photosensitization disease. Amorcsillin is a semi-synthetic aural penicillin antibiotic and produces side effects in order of fever, bronchospasm, serum sickness, exfoliative dermatitis, and anaphylaxis. Cephalosporine is a relatively less toxic, antibiotic derived from a fungus called Cephalosporium acremonium and, when administered as a parenteral preparation, causes local pain and thrombophlebitis and produces toxicity to the kidney. Imipenem is a sort of .beta.-lactam that usually causes nausea, vomiting, and often, seizures and CNS lesions. Aminoglycoside comprises a combination of different antibiotics isolated from the genus Streptomyces (except for gentamycin isolated from Micromonospora purpurea). All aminoglycoside antibiotics having a narrow safety margin lead to disorder in protein synthesis of bacterium and hence bactericidal action, and usually give rise to adverse side effects including cytotoxicity such as tinnitus and deafness, vertigo and walking difficulty.
Since analgesic and inflammatory agents are not limited in their use to one disease only but widely used for various diseases, there is a need for study and development of a non-narcotic analgesic without any side effect, and a therapeutic drug having tissue specificity with less side effects.